Whole exome sequencing identifies multiple diagnoses in congenital glaucoma with systemic anomalies. Clin Genet 2016 Oct;90(4):378-82
Date
06/09/2016Pubmed ID
27272408Pubmed Central ID
PMC5295561DOI
10.1111/cge.12816Scopus ID
2-s2.0-84988526168 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
The genetic basis of congenital glaucoma with systemic anomalies is largely unknown. Whole exome sequencing (WES) in 10 probands with congenital glaucoma and variable systemic anomalies identified pathogenic or likely pathogenic variants in three probands; in two of these, a combination of two Mendelian disorders was found to completely explain the patients' features whereas in the third case only the ocular findings could be explained by the genetic diagnosis. The molecular diagnosis for glaucoma included two cases with compound heterozygous or homozygous pathogenic alleles in CYP1B1 and one family with a dominant pathogenic variant in FOXC1; the second genetic diagnosis for the additional systemic features included compound heterozygous mutations in NPHS1 in one family and a heterozygous 18q23 deletion in another pedigree. These findings show the power of WES in the analysis of complex conditions and emphasize the importance of CYP1B1 screening in patients with congenital glaucoma regardless of the presence/absence of other systemic anomalies.
Author List
Reis LM, Tyler RC, Weh E, Hendee KE, Schilter KF, Phillips JA 3rd, Sequeira S, Schinzel A, Semina EVAuthors
Kathryn Hendee in the CTSI department at Medical College of Wisconsin - CTSIKala Schilter in the CTSI department at Medical College of Wisconsin - CTSI
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AllelesCytochrome P-450 CYP1B1
DNA Mutational Analysis
Exome
Female
Forkhead Transcription Factors
Glaucoma
Heterozygote
Humans
Infant
Male
Membrane Proteins
Pedigree
Sequence Analysis, DNA
